CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia

Soochow University

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute Lymphoblastic Leukemia, Adult B-Cell

Treatments: Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT03984968

SZCART01

Details and patient eligibility

About

This is a single-arm, open-label, single-center, phase I/II study to determine the safety and efficacy of CD19 CAR-T(ssCART-19) combined with autologous T cells engineered to express CD19, namely CD19+ feeding T cells (FTCs), as consolidation therapy in patients diagnosed with de novo Philadelphia chromosome-positive CD19+ B-ALL.

The study will contain the following sequential phases: screening, lymphocyte apheresis, induction, and consolidation chemotherapies combined with tyrosine kinase inhibitors. Once in complete response, patients will receive two to four cycles of ssCART-19s, namely one cycle of ssCART-19 infusion (CAR-T1) followed by one to three cycles of ssCART-19 and CD19+ FTC infusion (CAR-T2-4). The role of CD19+ FTCs is to mimic leukemia cells. Therefore, they are expected to stimulate in vivo expansion and persistence of ssCART-19.

Considering the limited number of lymphocytes obtained by a single apheresis from patients and cost-efficacy, in addition to safety, we will explore the range of biologically active doses of FTCs in a phase I study. Based on preclinical data, FTCs' stimulation of ssCART-19 at a ratio of 1:1 could achieve the best activation response, so a 5×10^6/kg dosage of FTCs was set as the initial dosage in the study, and lower doses were also evaluated. In phase I, FTCs will be administered at the dose of 5×10^6/kg, 3.25×10^6/kg, or 2×10^6/kg two hours after ssCART-19 infusion on day 1 and once again administered at the same dose on day 8. After ssCART-19 and FTCs infusion, adverse events (AEs) as the primary endpoints will be recorded for 6 months; efficacy as the secondary endpoint will be assessed by detecting molecular response for 6 months, PFS, and OS for 2 years.

In phase II, we will expand the study at optimal biological doses of FTCs and further evaluate the efficacy and safety of the innovative combination therapy of ssCART-19 and FTCs. The primary endpoint was the complete molecular response (CMR). The secondary endpoints were RFS, OS, and adverse events (AEs) of the patients.

Enrollment: 34 estimated patients

Sex: All

Ages: 15 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 15-65 years of age at the time of signing informed consent
• Diagnosed as de novo Philadelphia chromosome-positive CD19+ B-ALL
• Karnofsky performance status ≥ 60 or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Unable to find a suitable donor or for other reasons to undergo allogeneic hematopoietic stem cell transplantation during the study
• Ability and willingness to adhere to the study visit schedule and all protocol requirements
• Voluntarily sign informed consent forms

Exclusion criteria

• Unable to tolerate any kind of TKIs (including the first- and second-generation tyrosine kinase inhibitors) for a long period.
• Subjects who have positive mutation(s) of the ABL kinase domain and require the third-generation tyrosine kinase inhibitors for long-term therapies.
• Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN) and direct bilirubin > 1.5 × ULN
• Inadequate renal function defined by serum creatinine > 1.6 mg/dL
• International ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN
• Left ventricular ejection fraction < 50%
• Ongoing treatment with chronic immunosuppressants
• Significant comorbid conditions or diseases which, in the judgment of the investigator, would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions
• Known human immunodeficiency virus (HIV) positivity
• Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
• Subjects with second malignancies in addition to ALL
• Pregnant or lactating women, or subjects refusing to take effective contraception measures
• Other contraindications that are considered inappropriate to participate in this trial

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

34 participants in 4 patient groups

FTCs: High dose (Phase 1)

Experimental group

Treatment:

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

FTCs: Medium dose (Phase 1)

Experimental group

Treatment:

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

FTCs: Low dose (Phase 1)

Experimental group

Treatment:

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

FTCs: High dose (Phase 2)

Experimental group

Treatment:

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Biological: ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion